Investigating the Hypolipidemic Mechanism of Anthocyanins Combined with Allicin in Rats Using Network Pharmacology

Objectives: Using network pharmacology methods, investigate the potential lipid-lowering mechanism of the combination of anthocyanins and allicin in hyperlipidemic rats. Methods: Apply databases such as Pubchem, SwissTargetPrediction, TCMSP, DrugBank and BATMAN-TCM to predict potential targets for anthocyanins and allicin. Additionally, targets connected to hyperlipidemia were found in multiple databases (GeneCards, OMIM, Drugbank, and TTD). Upload the discovered drug-disease intersection targets into the database of STRING in order to construct a common target protein-protein interactions network (PPI). To find important targets, a PPI network analysis was built using Cytoscape 3.9.1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enriched and analyzed these common drug-disease targets. In order to further confirm the key targets of anthocyanins combined with allicin in hyperlipidemia, animal experiments were conducted. Results: There are 63 potential targets for the combined effect of anthocyanins and allicin on hyperlipidemia. The PPI topology analysis results found that TNF, IL-6, AKT1, PTGS2, GSK3B, EGFR, etc. are the main key targets. The main pathways included PI3K-Akt, JAK-STAT, Fluid shear stress and atherosclerosis, HIF-1and MAPK signaling pathway. The animal experiments results revealed that anthocyanins combined with allicin can improve blood lipid levels in hyperlipidemic rats and decrease the serum levels of inflammatory factors. Conclusion: Anthocyanins combined with allicin can intervene in hyperlipidemia through a variety of targets and pathways. This research offers a theoretical reference for the investigation of the pathogenesis of hyperlipidemia and the production of functional foods

Control of Lipid Metabolism by Adipocyte FGFR1-mediated Adipohepatic Communication During Hepatic Stress

Background: Endocrine FGF19 and FGF21 exert their effects on metabolic homeostasis through fibroblast growth factor receptor (FGFR) and co-factor betaKlotho (KLB). Ileal FGF19 regulates bile acid metabolism through specifically FGFR4-KLB in hepatocytes where FGFR1 is not significant. Both FGF19 and FGF21 activate FGFR1-KLB whose function predominates in adipocytes. Recent studies using administration of FGF19 and FGF21 and genetic ablation of KLB or adipocyte FGFR1 indicate that FGFR1-KLB mediates the response of adipocytes to both FGF21 and FGF19. Here we show that adipose FGFR1 regulates lipid metabolism through direct effect on adipose tissue and indirect effects on liver under starvation conditions that cause hepatic stress. Methods: We employed adipocyte-specific ablations of FGFR1 and FGFR2 genes in mice, and analyzed metabolic consequences in adipose tissue, liver and systemic parameters under normal, fasting and starvation conditions. Results: Under normal conditions, the ablation of adipose FGFR1 had little effect on adipocytes, but caused shifts in expression of hepatic genes involved in lipid metabolism. Starvation conditions precipitated a concurrent elevation of serum triglycerides and non-esterified fatty acids, and increased hepatic steatosis and adipose lipolysis in the FGFR1-deficient mice. Little effect on glucose or ketone bodies due to the FGFR1 deficiency was observed. Conclusions: Our results suggest an adipocyte-hepatocyte communication network mediated by adipocyte FGFR1 that concurrently dampens hepatic lipogenesis and adipocyte lipolysis. We propose that this serves overall to mete out and extend lipid reserves for neural fuels (glucose and ketone bodies), while at the same time governing extent of hepatosteatosis during metabolic extremes and other conditions causing hepatic stress

A tuber mustard AP2/ERF transcription factor gene, BjABR1, functioning in abscisic acid and abiotic stress responses, and evolutionary trajectory of the ABR1 homologous genes in Brassica species

The AP2/ERF superfamily of transcription factors is one of the largest transcription factor families in plants and plays an important role in plant development processes and stress responses. In this study, BjABR1, an AP2/ERF superfamily gene, from tuber mustard (Brassica juncea var. tumida Tsen et Lee), sharing high amino acid sequence similarity with the AtABR1 (Arabidopsis thaliana AP2-like abscisic acid repressor 1) gene, were performed functional research, and the ABR1 homologous genes in Brassica species were identified and performed phylogenetic analysis. The promoter sequence of BjABR1 contained many phytohormone- and stress-related cis-elements; ABA (abscisic acid) and abiotic stresses can induce BjABR1 expression in tuber mustard; overexpression of BjABR1 in Arabidopsis can alleviate plant sensitivity to ABA and salt and osmotic stresses, and the alleviation may be due to changes in stress/ABA-induced gene expression. These results indicated that BjABR1 functions in ABA and abiotic stress responses. By BLAST searches against the genome database of five Brassica species (three diploids, B. rapa, B. nigra, and B. oleracea, and two allotetraploid, B. juncea and B. napus) using the protein sequence of AtABR1, 3, 3, 3, 6, and 5 ABR1 homologous genes in B. nigra, B. rapa, B. oleracea, B. juncea, and B. napus were identified, respectively, and they shared high sequence similarity. By sequence analysis, annotation mistakes of the protein-coding regions of two ABR1 homologous genes, GSBRNA2T00134741001 and BjuB007684, were found and corrected. Then, the evolution analysis of these ABR1 homologous genes showed that the ancestor of the three diploid species had three ABR1 homologous genes and each diploid inherited all the three genes from their ancestor; then, allotetraploid B. juncea inherited all the six genes from B. rapa and B. nigra with no gene lost, while allotetraploid B. napus inherited all the three genes from B. oleracea and two genes from B. rapa with one gene lost, indicating that ABR1 homologous genes possessed greater hereditary conservation in Brassica species. The ABR1 homologous genes between B. rapa and B. oleracea shared much higher sequence similarity compared to that of B. nigra in diploid species, indicating that ABR1 homologous genes in B. nigra had experienced more rapid evolution, and B. rapa and B. oleracea may share closer relationship compared to B. nigra. Moreover, the spatial and temporal expression analysis of six ABR1 homologous genes of tuber mustard showed that they possessed different expression models. These results imply that ABR1 homologous genes are important to Brassica plants, and they may possess similar function in ABA and abiotic stress responses but play a role in different tissues and growing stages of plant. This study will provide the foundation to the functional research of ABR1 homologous genes in the Brassica species and help to reveal and understand the evolution mechanisms of Brassica species

Differential Specificity of Endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in Complex with KLB

Background: Recent studies suggest that betaKlotho (KLB) and endocrine FGF19 and FGF21 redirect FGFR signaling to regulation of metabolic homeostasis and suppression of obesity and diabetes. However, the identity of the predominant metabolic tissue in which a major FGFR-KLB resides that critically mediates the differential actions and metabolism effects of FGF19 and FGF21 remain unclear. Methodology/Principal Findings: We determined the receptor and tissue specificity of FGF21 in comparison to FGF19 by using direct, sensitive and quantitative binding kinetics, and downstream signal transduction and expression of early response gene upon administration of FGF19 and FGF21 in mice. We found that FGF21 binds FGFR1 with much higher affinity than FGFR4 in presence of KLB; while FGF19 binds both FGFR1 and FGFR4 in presence of KLB with comparable affinity. The interaction of FGF21 with FGFR4-KLB is very weak even at high concentration and could be negligible at physiological concentration. Both FGF19 and FGF21 but not FGF1 exhibit binding affinity to KLB. The binding of FGF1 is dependent on where FGFRs are present. Both FGF19 and FGF21 are unable to displace the FGF1 binding, and conversely FGF1 cannot displace FGF19 and FGF21 binding. These results indicate that KLB is an indispensable mediator for the binding of FGF19 and FGF21 to FGFRs that is not required for FGF1. Although FGF19 can predominantly activate the responses of the liver and to a less extent the adipose tissue, FGF21 can do so significantly only in the adipose tissue an

Underwater Target Localization and Synchronization for a Distributed SIMO Sonar with an Isogradient SSP and Uncertainties in Receiver Locations

A distributed single-input multiple-output (SIMO) sonar system is composed of a sound source and multiple underwater receivers. It provides an important framework for underwater target localization. However, underwater hostile environments bring more challenges for underwater target localization than terrestrial target localization, such as the difficulties of synchronizing all the underwater receiver clocks, the varying underwater sound speed and the uncertainties of the locations of the underwater receivers. In this paper, we take the sound speed variation, the time synchronization and the uncertainties of the receiver locations into account, and propose the underwater target localization and synchronization (UTLS) algorithm for the distributed SIMO sonar system. In the distributed SIMO sonar system, the receivers are organized in a star topology, where the information fusion is carried out in the central receiver (CR). All the receivers are not synchronized and their positions are known with uncertainties. Moreover, the underwater sound speed is approximately modeled by a depth-dependent sound speed profile (SSP). We evaluate our proposed UTLS algorithm by comparing it with several benchmark algorithms via numerical simulations. The simulation results reveal the superiority of our proposed UTLS algorithm

Evolution and Efficiency Assessment of Pesticide and Fertiliser Inputs to Cultivated Land in China

Excessive use of pesticides and fertilisers has been a key issue limiting sustainable agricultural development. China is a typical pesticide- and chemical-fertiliser-dependent agricultural production area. We have matched the target indicators related to sustainable agricultural development (SDG1 and SDG2) and analysed the gap between China and four developed countries in terms of fertiliser and pesticide use intensity and efficiency from 2002 to 2016. We have used an improved Logarithmic Mean Divisia Index model and cluster analysis to identify the factors and effects driving increased pesticide and fertiliser inputs in China, and we discuss the exploratory effects of different provinces in reducing pesticide and fertiliser application and increasing efficiency. The findings reveal that (1) China is a typical pesticide- and fertiliser-dependent agricultural production area. The average combined fertiliser application efficiency in China from 2002 to 2016 was only 28% of that of the Netherlands, and the country’s average combined pesticide application efficiency was only 35% of that of the USA. (2) The most important of the three main drivers of the increase in pesticide and fertiliser inputs in China is the value added of the primary industry, contributing 56% for the period 2007–2016. (3) Further analysis at the provincial level according to four types—high-intensity high-yield type, high-intensity low-yield type, low-intensity high-yield type, and low-intensity low-yield type—clarified the provinces that should be focused on at the national level in terms of pesticide and fertiliser application reduction and efficiency increase in the future

Development Trend and Driving Factors of Agricultural Chemical Fertilizer Efficiency in China

In China, a high input of chemical fertilizers is currently required for a relatively low increase in agricultural production, and this has resulted in prominent nonpoint source pollution and problems related to the quality of agricultural products. These phenomena threaten China’s implementation of United Nations Sustainable Development Goal 2 (SDG-2). To explore agricultural chemical fertilizer efficiency and the factors driving the growth in chemical fertilizer use in China, as based on an international comparative analysis of China’s chemical fertilizer input, the development trend in the application level and the efficiency in the use of chemical fertilizer in China were subject to time series analysis, and the factors influencing change were identified and analyzed using the Logarithmic Mean Divisia Index (LMDI). The results show that: (1) The gap in agricultural chemical fertilizer efficiency is still large when comparing China with modern agricultural countries, and excessive fertilizer input is still a major problem. (2) The continuous growth in the total amount of chemical fertilizer applied in China during the past 18 years has contributed to the increase in chemical fertilizer application intensity, which provided a cumulative contribution of 85.52%, with smaller contributions from the planting structure and crop sown area. Based on the analysis of fertilizer application, the chemical fertilizer application intensity of the main grain crops was the most significant factor, accounting for about a 40.00% cumulative contribution. (3) Since 2015, the total amount of chemical fertilizers has been reduced through gradually improving the utilization rate of chemical fertilizers, reducing the application intensity of chemical fertilizers, and implementing the fallow rotation system and other measures. Of these, the reduction in application intensity was the most effective at reducing the overall amount of applied fertilizer. To meet the target for achieving sustainable agricultural development, China must still reduce its use of chemical fertilizers by at least 21.80 million tons. Based on the results of current measures and international experience, some suggestions for reducing fertilizer usage are provided

Postprocessing Study for the Controllable Structures of Ceramic Green Parts Realized by a Flexible Binder Jetting Printing (BJP) Solution

For indirect ceramic additive manufacturing (AM), green parts’ initial densities are low, limiting the postprocessing strengthening under atmospheric pressure. This study employed binder jetting printing (BJP) based on the polycondensation curing of urea-formaldehyde resin to produce series of Al2O3 green specimens with controllable structures. Further, an integrated postprocessing procedure, including the sequential stages of presintering, ceramic slurry infiltration, and final sintering, was conducted on these green specimens with designed structural characteristics for verifying strengthening mechanism. Using a self-developed BJP machine system and the related material which are flexible in process, this study printed green specimens with strong bonding (flexural strength above 6.84 MPa), additionally can regulate their initial densities within the wide range between 21.7%∼43.9%. Infiltrated with ceramic slurry, low-density green specimens were significantly strengthened via final sintering, realizing final densities, flexural strength, and compressive strength of 73.2%, 43.15 MPa, and 331.17 MPa, respectively. In comparison, high-density specimens performing poor infiltration obtained limited density increment after final sintering, but better mechanical properties and surface strengthening were realized, exhibiting final densities, flexural strength, comprehensive strength, surface roughness Ra, and Vickers hardness of 70.1%, 63.22 MPa, 450.18 MPa, 9.73 μm, and 4.58 GPa, respectively. In summary, this study is helpful to provide the technical reference for custom AM ceramic green parts and the postprocessing optimization